Dysregulation of immune checkpoint LAG3 in mice exposed to silica

Silica exposure can cause silicosis, and its pathogenesis is not fully understood. This study investigates the role of immune checkpoint lymphocyte activation gene 3 (LAG3) in silicosis. Mice were intratracheally exposed to silica, and tissues were collected and analyzed after 7 and 28 days. Additionally, peripheral blood samples were also collected from silicosis patients. The mRNA and protein expression levels of LAG3 in various tissues were quantified using qRT-PCR and western blot techniques. The localization of LAG3 in the lung, spleen, thymus and hilar lymph nodes was visualized by immunochemistry. Our data showed that silica exposure induced systemic changes in LAG3 expression in an organ-specific manner. In mouse lungs, LAG3 levels were significantly upregulated after silica exposure. In mouse spleen, LAG3 expression changed only during early stage of silica exposure. In mouse thymus, the level of LAG3 decreased during early stage of silica exposure but reversed to increase during late stage. In mouse hilar lymph nodes, expression of LAG3 increased significantly. A marked increase in the concentration of soluble LAG3 was observed in the plasma of mice exposed to silica. Plasma soluble LAG3 levels in silicosis patients were found to be significantly higher than healthy controls. These findings suggest that LAG3 may be involved in the pathogenesis of silicosis and that immune disorders in lung tissue may further affect systemic immune homeostasis.